A cross‐sectional study of outcomes for patients undergoing mechanical thrombectomy for pulmonary embolism during 2018–2022: Insights from the PINC AI Healthcare Database

Abstract Background and Aims Mechanical thrombectomy (MT) treatments for pulmonary embolism (PE) have yet to be compared directly. We aimed to determine if patient outcomes varied following treatment of PE with different MT devices. Methods All PE encounters with an index treatment of MT between January 2018 and March 2022 were analyzed for in‐hospital mortality, discharge to home, and 30‐day readmission outcomes in the PINC AI™ Healthcare Database. MT devices used in each encounter were extracted from hospital charge description free‐text fields using keyword text and fuzzy matching. Unadjusted and adjusted logistic regression was used to model outcomes by device. Results A total of 5893 encounters were identified using MT as the sole index PE treatment and 1812 using MT with another treatment. Of these, 41% had insufficient information to identify the devices used (unspecified MT), 33% used the FlowTriever System (large‐bore volume‐controlled aspiration MT), 23% the Indigo System (continuous aspiration MT), and 3% some other MT. Large‐bore volume‐controlled aspiration MT was used with other treatments 13% of the time compared with 23% and 39% for unspecified MT and continuous aspiration MT, respectively. Adjusted logistic regression modeling revealed the odds of in‐hospital mortality were significantly higher for patients treated with unspecified MT ([OR] = 1.42, 95% confidence interval [CI]: [1.10–1.83], p = 0.008) or continuous aspiration MT (OR = 1.63, 95% CI: [1.21–2.19], p = 0.001) compared with large‐bore volume‐controlled aspiration MT. Discharge to home was significantly lower in these same groups (OR = 0.84, 95% CI: [0.73–0.96], p = 0.01, and OR = 0.63, 95% CI: [0.53–0.74], p < 0.001, respectively), but readmission risks at 30 days were comparable (OR = 1.08, 95% CI: [0.84–1.38], p = 0.56, and OR = 1.20, 95% CI: [0.89–1.62], p = 0.24, respectively). Conclusion PE outcomes and treatment patterns differ significantly based on the type of MT utilized. Clinical studies directly comparing MT treatments are needed to further understand optimal treatment of PE.


| INTRODUCTION
Pulmonary embolism (PE) is an acute occlusion of pulmonary artery flow, typically resulting from thrombus embolized from a deep vein thrombosis, that occurs in about 115 per 100,000 people in the United States. 1 The increase in pulmonary artery pressure resulting from PE can cause right ventricle pressure overload and ultimately fatal right heart failure, particularly within the first 72 h of development. 2Historically, PE has been treated with anticoagulation (AC), systemic thrombolysis (ST), or surgical embolectomy.However, the development and use of catheter-directed therapies has increased dramatically in the last two decades.For example, in a national sample of Medicare claims data from 2004 to 2016, Gayou et al. reported a 10-fold increase in the proportion of PEs treated with catheter-directed therapies. 3ndomized controlled trial data demonstrated that ST reduces PE mortality or hemodynamic decompensation more than AC alone, but does so with an increased risk of major bleeding and hemorrhagic stroke. 4Subsequently, two types of catheter directed therapies are being investigated with the goal of lowering the risks associated with PE treatment: catheter-directed thrombolysis (CDT) and mechanical thrombectomy (MT). 5,6While CDT treatments have been shown in a limited randomized study to achieve similar clinical outcomes, 7 the variety of MT treatments have not yet been compared directly, despite their utilization increasing more than fourfold in the Nationwide Inpatient Sample (NIS) between 2010 and 2018. 8Consequently, MT is often assessed as a class, particularly in real-world data sources where procedure codes do not distinguish between the various MT devices. 9However, data from a meta-analysis suggested significant heterogeneity in mortality, major bleeding, and combined use with thrombolytics following treatment with different types of MT. 10 Additional evaluation of PE patient outcomes at the device level following MT treatment is warranted to explore these findings.
The PINC AI™ Healthcare Database (PHD) is a national, all-payer database that contains procedural coding data as well as chargemaster (CDM) data, allowing for identification of specific devices used within a hospital encounter.Using this database, we aimed to determine what, if any, differences existed in patient outcomes following MT treatment of PE with different devices to better understand the optimal treatment of PE using MT.

| Data source
The PHD is a national, all-payer database that contains roughly 25% of all inpatient hospitalizations in the United States. 11 analyzed at the encounter level and excluded encounters where the patient was less than 18 years old, pregnant, or contained intrahospital transfers that did not allow the data to be distinguished at the encounter level.Cost data were adjusted for inflation using healthcare inflation data from the US Labor Department's Bureau of Labor Statistics. 12Inflation rates were aggregated quarterly, taking the maximum rate per quarter, and applied to total patient costs from the cohorts.

| Device identification and grouping
Two MT devices are currently indicated for use in the treatment of PE in the United States: the Indigo System (Penumbra Inc) and the FlowTriever System (Inari Medical).The Indigo System utilizes pumpdriven continuous aspiration through 6-16 French catheters for thrombus removal (continuous aspiration MT) while the FlowTriever System employs a manually loaded 60 cc vacuum syringe to generate suction through 16-24 French catheters (large-bore volumecontrolled aspiration MT).Note that the 16-French Indigo System catheter was released after the data window for this work and so is not represented in this analysis.Identification of the device(s) used in each encounter was extracted from hospital CDM description freetext fields using a combination of keyword text matching (e.g., "FlowTriever") and fuzzy matching (e.g., "FlowTr*ver") for these and other MT device names used in the treatment of PE.In many cases, MT was listed in the International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD-10-PCS) codes, but no further information regarding the specific MT device used was available in the CDM.Results for this population are shown under the category "unspecified MT."

| Outcomes, procedures, and adjustment variables
The three clinical outcomes examined in this analysis included inhospital all-cause mortality, discharge to home, and inpatient hospital readmission within 30 days of discharge.Discharge status, including mortality and discharge to home, are included directly in the PHD.Readmission is a derived variable that is only captured if a patient is readmitted to the same hospital or hospital system.
A combination of ICD-10-PCS codes and the detailed billing CDM were used to identify PE encounters with interventions by surgery, MT, CDT, or ST (Supporting Information S1: Table S1).The first procedure to occur during an encounter established the index procedure day.To reduce confounding from multiple procedures occurring across a potentially long hospitalization and focus the analysis on procedures most likely to be treating the index PE, only procedures conducted on the index procedure day or within the following 4 days were analyzed.Index day interventions without any other procedure types billed within this window were labeled as standalone.Index day interventions with additional procedure types billed within this window were defined as combination therapy.
International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes were used to examine conditions and diagnoses present during each encounter.ICD-10-CM codes used in this analysis were selected based on commonly accepted code sets [13][14][15] and are shown in Supporting Information S1: Table S1.

| Statistical analysis
The goal of this analysis was to compare three  S2.
All statistical tests were two-sided with an alpha level of 0.05, conducted in R studio (Version 2023.12.1).that used MT as the sole index day PE treatment and an additional 1812 encounters using MT in combination with another treatment (Figure 1).5.5%-6.6%),and patients treated with MT combined with a nonthrombolytic therapy more often presented with sepsis (14% vs.
To explore potential differences in the use of combination therapy between types of MT treatments, keyword text, and fuzzy matching techniques were applied to the hospital CDM field within the PHD to further classify patient treatment by device used.As shown in Figure 2, 41% of MT encounters contained appropriate ICD-10-PCS codes but insufficient device-level hospital charge information for further classification (unspecified MT), 33% of encounters utilized large-bore volume-controlled aspiration MT, 23% continuous aspiration MT, and 3.1% some other type of MT system (72% of these being Angiovac, Angiodynamics).Due to their heterogeneity and limited number, encounters in the "other" category were excluded from subsequent analyses.Combination therapy usage varied by MT device.Large-bore volume-controlled aspiration MT was used in combination only 13% of the time compared with 23% and 39% for unspecified MT and continuous aspiration MT, respectively.Similarly, thrombolytics were used in conjunction with  Since standalone MT treatment is likely to be associated with the fewest treatment decision confounders, we next examined the summary statistics of patients receiving standalone MT by device to identify any differences in outcomes or patient characteristics (Table 2).Demographic and comorbidity characteristics were mostly comparable in patients across device types except that patients treated with continuous aspiration MT were more frequently Hispanic (7.8% vs. 3.3%-5.2%)or diagnosed with peripheral vascular disease (13% vs. 6.0%-7.5%)and less frequently obese (33% vs. 41%).In-hospital mortality rates varied by device, ranging from 4.9% for large-bore volume-controlled aspiration MT to 8.7% for continuous aspiration MT.Discharge to home among those without inhospital mortality was lowest for patients treated with continuous aspiration MT (57% vs. 64%-68%), but 30-day readmission risks were similar between device treatment groups (6.1%-7.7%).
However, no explanatory differences in characteristics were observed between MT devices in patients who died in-hospital or those who were alive at discharge.To more fully explore the outcome disparities observed between patients receiving treatment with different MT devices, multivariable logistic regression was used to model in-hospital mortality, discharge to home, and 30-day readmission adjusting for known confounders (Figure 3).After adjusting for differences in patient characteristics and comorbidities, the odds of in-hospital mortality remained significant and higher for patients treated with an  S3).

| DISCUSSION
This analysis compared device-level differences in outcomes and treatment patterns among hospitalized PE patients treated with MT in a national all-payer database.The frequency and pattern of combination therapy differed between devices-large-bore volumecontrolled MT was used 43%-67% less often in combination and 63%-76% less often with thrombolysis than other MT treatments.
7][18] and a meta-analysis of aspiration MT (3.6%). 10This is to some degree expected based on the heterogeneous disease severity, comorbidities, and additional procedures or diagnoses unaccounted for in real-world data compared with clinical trial data.However, the mortality rates for MT alone in the current analysis also appear lower than the 9.1%-13% in-hospital mortality published in recent real-world analyses of PE in the NIS and Nationwide Readmissions Database. 8,9,14,19This may reflect variation in the populations in each database, the timeframes evaluated, and most likely differences in treatment categorization in each study (e.g., in-hospital mortality in this analysis was 8%-17% when including patients receiving multiple treatments, including thrombolytics).
However, it is of great interest that, after adjusting for discrepancies in relevant population, admission point of origin, and hospital characteristics and accounting for the significant variation observed in the use of combination In-hospital mortality, N (%) 106 (  20,21 Whether these patterns indicate a relative lack of standalone effectiveness for continuous aspiration MT or rather reflect historical practice trends is unclear from these data alone.
Besides the possibility of a potential class effect difference between large-bore volume-controlled aspiration MT and continuous aspiration MT, the patient populations may have fundamental differences that are not accounted for in the current analysis.For example, although the patients had acute PE as a diagnosis, it is possible that some of the MT treatment was used for non-PE pathology, such as intracardiac or deep vein thrombus, skewing the results.
The findings of this study are strengthened by a large sample size and the use of explicit device name mentions to enable assessment of device-level outcomes.However, the limitations of this data set and analytic approach provide important context for interpreting these results.First, selection bias and the potential for coding errors are inherent limitations with any retrospective administrative database analysis.We have reduced some of the potential for procedure coding errors by including CDM-named device data in our analysis.However, at least half of these data contained no explicit device name and may consequently not be representative of use throughout the entire population.Further, limited clinical details (e.g., disease severity, treatment timing, etc.) preclude meaningful analysis of relative disease severity and post-procedural complications such as bleeding and treatment deterioration.Third, our modeling adjusted for observed differences in our patient populations, however, unknown confounders and disease characteristics or procedures not analyzed in these data may have influenced the differences observed.

| CONCLUSION
More than 1300 hospitals/healthcare systems from 45 US states and the District of Columbia have contributed to the database since 2000.The PHD contains data that are deidentified and HIPAA-compliant in accordance with the HIPAA Privacy Rule, per 45 CFR 164.514(b)(1) through the "Expert Determination" method.As such, this analysis does not meet the definition of human subjects research requiring investigational review board (IRB) review and patient consent.The PHD contains information about patient characteristics, drugs, devices and other treatments, disease states, costs and resource utilization, and clinical outcomes.Importantly, the PHD also contains the CDM, a comprehensive table of items billable to a hospital patient or health insurance provider.It includes hospital services, medical procedures, equipment fees, supplies, and drugs, documented by service day.The charge description is an optionally completed free-text field that can be used to extract mentions of specific medical devices and treatments.Data used in this study included inpatient hospital encounters with a PE diagnosis in any position, where the patient was discharged between January 2018 and March 2022.Data were clinical outcomes for different types of MT treatments.Descriptive statistics are shown for encounters treated with MT alone (no other treatments within the 4 days following the index procedure), and MT in combination with other treatments occurring on the index procedure day or within the following 4 days.The PHD only contains information on treatment timing by day, limiting more detailed description of the clinical decision pathway.When MT was the only index treatment, descriptive statistics are shown for large-bore volume-controlled aspiration MT, continuous aspiration MT, and unspecified MT.Logistic regression was used to model in-hospital mortality, discharge to home, and 30-day readmission.Discharge to home and 30-day readmission were modeled for patients who did not die in hospital.Unadjusted and adjusted results are shown; the demographics and conditions added to the logistic model are listed in Supporting Information S1: Table

A
total of 426,194 hospitalizations with acute PE were identified in the PHD between January 2018 and March 2022.Of these, 13,916 were excluded based on age (<18 years), pregnancy, or as intrahospital transfers leading to duplicate database encounters.From the remaining population, ICD-10-PCS codes identified 5893 encounters F I G U R E 1 Analysis population.After excluding pregnant patients, those younger than 18 years of age, and *patients with intrahospital transfers leading to duplicate database encounters, all patients hospitalized with acute PE between January 2018 and March 2022 receiving mechanical thrombectomy treatment either alone or in combination with other therapies comprised the analysis population.Patients without treatment codes, "Other," were presumed to have received AC therapy.AC, anticoagulation; CDT, catheter-directed thrombolysis; MT, mechanical thrombectomy; PE, pulmonary embolism; ST, systemic thrombolysis.
29% of continuous aspiration MT encounters, 19% of unspecified MT encounters, and 7.4% of large-bore volume-controlled aspiration MT encounters.
unspecified MT treatment (odds ratio [OR] = 1.42, 95% confidence interval [CI]: [1.10-1.83],p = 0.008) or continuous aspiration MT (OR = 1.63, 95% CI: [1.21-2.19],p = 0.001) compared with large-bore volume-controlled aspiration MT.In contrast, the odds of being discharged to home were significantly lower in these same groups (OR = 0.84, 95% CI: [0.73-0.96],p = 0.01 for unspecified MT and OR = 0.63, 95% CI: [0.53-0.74],p < 0.001 for continuous aspiration MT) compared with large-bore volume-controlled aspiration MT.After adjustment, 30-day readmission risks remained comparable between groups (OR = 1.08, 95% CI: [0.84-1.38],p = 0.56 for unspecified MT and OR = 1.20, 95% CI: [0.89-1.62],p = 0.24 for continuous aspiration MT).Evaluation of admission point of origin and hospital-level characteristics in each group revealed small differences which, when included in additional modeling, yielded similar results (Supporting Information S1: Table Frequency of standalone MT and use in combination with non-MT treatments by device.Frequency of standalone treatment (gray) and use in combination with another non-MT treatment (blue) by MT device.CDT, catheter-directed thrombolysis; MT, mechanical thrombectomy; ST, systemic thrombolysis.device-leveltreatment, but patients receiving either unspecified MT or continuous aspiration MT had significantly higher adjusted odds ratios (1.42 and 1.63) for dying in-hospital and significantly lower adjusted odds ratios (0.84 and 0.63) for being discharged to home compared with those treated with large-bore volume-controlled MT.
PE outcomes and treatment patterns differ significantly based on the type of MT utilized.Rates of in-hospital mortality and discharge to home were significantly worse in patients treated with continuous aspiration MT versus large-bore volume-controlled MT.Continuous aspiration MT was also associated with the highest rates of combination therapy and thrombolytic use.Clinical studies directly comparing MT treatments are needed to further understand optimal treatment of PE using MT.

Table 1
details the summary statistics of patients receiving MT alone as well as those receiving another therapy in combination with MT.Patient demographic characteristics and comorbidities were Mechanical thrombectomy summary statistics by therapy type.
Standalone mechanical thrombectomy summary statistics by device.
and 63% higher adjusted odds of dying during the index admission compared with patients treated with large-bore volume-controlled aspiration MT.The specific causes of the disparities in mortality between MT devices are unclear from this analysis and warrant detailed study.Patient characteristics or other treatment factors not accounted for in our analysis may have influenced the T A B L E 2 Standalone mechanical thrombectomy summary statistics by device and in-hospital mortality.
Second, continuous aspiration MT is used in combination with thrombolytics much more often (29% vs. 7.4%-19%) than other MT treatments.This aligns with other published reports of real-world continuous aspiration MT usage in combination with thrombolytics in about 20% of patients.